Content and organization of the human Ig VH locus: definition of three new VH families and linkage to the Ig CH locus.
Jeffrey E. Berman,S. J. Mellis,Roberta R. Pollock,Cassandra L. Smith,Heikyung Suh,B. Heinke,C. Kowal,Urvashi Surti,Leonard Chess,C. R. Cantor +9 more
TLDR
The first report of the physical linkage of the variable and constant loci of a human Ig gene family is provided by demonstrating that the most proximal known human VH segments lie within 100 kb of the constant region locus.Abstract:
We present a detailed analysis of the content and organization of the human immunoglobulin VH locus. Human VH genes representing five distinct families were isolated, including novel members belonging to two out of three of the known VH gene families (VH1 and VH3) as well as members of three new families (VH4, VH5, and VH6). We report the nucleotide sequence of 21 novel human VH genes, many of which belong to the three new VH gene families. In addition, we provide a preliminary analysis of the organization of these gene segments over the full extent of the locus. We find that the five multi-segment families (VH1-5) have members interspersed over nearly the full 1500-2000 kb of the VH locus, and estimate that the entire heavy chain locus covers 2500 kb or less. Finally, we provide the first report of the physical linkage of the variable and constant loci of a human Ig gene family by demonstrating that the most proximal known human VH segments lie within 100 kb of the constant region locus.read more
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Transgenic mice containing a human heavy chain immunoglobulin gene fragment cloned in a yeast artificial chromosome.
Ted K. Choi,Paul W. Hollenbach,Barbara E. Pearson,Roanna M. Ueda,Gregory N. Weddell,Carole G. Kurahara,Clive S. Woodhouse,Robert M. Kay,Jeanne F. Loring +8 more
TL;DR: Co–lipofection may prove to be a highly–successful means of producing transgenic mice containing large gene fragments in YACs, as demonstrated by expression of the YAC–borne immunoglobulin gene fragment.
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Human organ-specific autoimmune disease. Molecular cloning and expression of an autoantibody gene repertoire for a major autoantigen reveals an antigenic immunodominant region and restricted immunoglobulin gene usage in the target organ.
G D Chazenbalk,Stefano Portolano,Diego Russo,J S Hutchison,Basil Rapoport,Sandra M. McLachlan +5 more
TL;DR: The molecular cloning of the genes for 30 high-affinity, IgG-class human autoantibodies to TPO from thyroid-infiltrating B cells suggests that there is restriction in H and L chain usage in relation to the interaction with specific antigenic domains in human, organ-specific autoimmune disease.
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VH4-21, a human VH gene segment overrepresented in the autoimmune repertoire.
Virginia Pascual,J D Capra +1 more
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Immunoglobulin heavy chain gene expression in peripheral blood B lymphocytes.
TL;DR: In this article, a cDNA library for IgM heavy chain variable regions was prepared from unmanipulated peripheral blood lymphocytes of two healthy people and partial sequencing of 103 clones revealed VH gene family use and complete CDR3 and JH sequences.
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The structural basis of germline-encoded VH3 immunoglobulin binding to staphylococcal protein A.
TL;DR: The results demonstrate that among human IgM, specificity for SPA is encoded by at least 11 different VH3 germline genes, and like the T cell superantigens, SPA likely binds to residues in the VH framework region, outside the classical antigen-binding site of the hypervariable loops.